Our previous studies have suggested that mitochondrial dysfunction causes oxidative genomic DNA damage and contributes to tumorigenesis. Oxygen is necessary for aerobic life but it also serves as the essential substrate for reactive oxygen species that can cause biological damage. We are currently using environmental and genetic methods to modulate oxygen homeostasis and to examine their effect on energy metabolism, tumorigenesis, and cardiovascular disease. We are also examining adaptive mechanisms by which cells of neoplastic or cardiovascular origin survive under oxidative or other toxic stress conditions.